ArticleMolecular neurobiology2024
USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
- Hepatic Lipid Stress Drives Metabolic Dysfunction-Associated Steatohepatitis Progression through FTO O-GlcNAcylation-Induced m6A Demethylation of HRAS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- METTL1/WDR4 Complex: A Novel Epitranscriptomic Target at the Crossroads of RNA Methylation and Drug Discovery.Journal of medicinal chemistry · 2026Review
- E3 ligase LMO7 promotes ALKBH2 ubiquitination to sensitize MGMT-deficient glioblastoma to temozolomide.Cell death & disease · 2026Article
- The Role of NMedComm · 2026Review
- Lactylation of PTBP1 drives a pro-apoptotic positive feedback loop in microglia following oxygen-glucose deprivation/reoxygenation-induced injury.Cell death & disease · 2026Article
- The role of N6-methyladenosine associated genes in ischemic stroke risk: interplay with environmental factors.Journal of thrombosis and thrombolysis · 2026Review
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- Glycine Alleviates HMolecular neurobiology · 2026Article
- IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting Epigenetics in Ischemic Stroke: From Mechanisms to Therapeutics.Current neuropharmacology · 2026Review
- Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.Molecular and cellular biochemistry · 2025Review
- Sirtuins Contribute to the Migraine-Stroke Connection.International journal of molecular sciences · 2025Review
- Transcriptomic analysis of the m6A reader YTHDF2 in the maintenance and differentiation of human embryonic stem cells.Stem cells (Dayton, Ohio) · 2025Article
- Genome-wide analysis of lncRNA m6A methylation in the mouse cortex after repetitive mild traumatic brain injury.BMC genomics · 2025Article
- USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma.Cell death discovery · 2025Article
- Lactylation and Ischemic Stroke: Research Progress and Potential Relationship.Molecular neurobiology · 2025Review
- USP18 promote tumor immune evasion in pancreatic cancer through enhancing autolysosome-mediated degradation of MHC-I.American journal of cancer research · 2025Article
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Post-Translational Modifications of RNA-Modifying Proteins in Cellular Dynamics and Disease Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.